Feasibility and effectiveness assessment of sars-cov-2 antigenic tests in mass screening of a pediatric population and correlation with the kinetics of viral loads

The gold standard for diagnosis of SARS-CoV-2 infection has been nucleic acid amplification tests (NAAT). However, rapid antigen detection kits (Ag-RDTs), may offer advantages over NAAT in mass screening, generating results in minutes, both as laboratory-based test or point-of-care (POC) use for clinicians, at a lower cost. We assessed two different POC Ag-RDTs in mass screening versus NAAT for SARS-CoV-2 in a cohort of pediatric patients admitted to the Pediatric Emergency Unit of IRCCS—Polyclinic of Sant’Orsola, Bologna (from November 2020 to April 2021). All patients were screened with nasopharyngeal swabs for the detection of SARS-CoV-2-RNA and for antigen tests. Results were obtained from 1146 patients. The COVID-19 Ag FIA kit showed a baseline sensitivity of 53.8% (CI 35.4–71.4%), baseline specificity 99.7% (CI 98.4–100%) and overall accuracy of 80% (95% CI 0.68–0.91); the AFIAS COVID-19 Ag kit, baseline sensitivity of 86.4% (CI 75.0–93.9%), baseline specificity 98.3% (CI 97.1–99.1%) and overall accuracy of 95.3% (95% CI 0.92– 0.99). In both tests, some samples showed very low viral load and negative Ag-RDT. This disagreement may reflect the positive inability of Ag-RDTs of detecting antigen in late phase of infection. Among all cases with positive molecular test and negative antigen test, none showed viral loads > 106 copies/mL. Finally, we found one false Ag-RDTs negative result (low cycle thresholds; 9 × 105 copies/mL). Our results suggest that both Ag-RDTs showed good performances in detection of high viral load samples, making it a feasible and effective tool for mass screening in actively infected children

Gene Modulation by Peptide Nucleic Acids (PNAs) Targeting microRNAs (miRs)

Since non-viral gene therapy was developed and employed in different in vitro and in vivo experimental systems as an effective way to control and modify gene expression, RNA has been considered as a molecular target of great relevance (Li &Huang, 2008, López-Fraga et al., 2008). In combination with standard chemotherapy, the siRNA therapy can reduce the chemoresistance of certain cancers, demonstrating its potential for treating many malignant diseases. Examples of RNA sequences to be targeted for therapeutic applications are mRNAs coding oncoproteins or RNA coding anti-apoptotic proteins for the development of anti-cancer therapy. In the last years, progresses in molecular biology have allowed to identify many genes Coding for small non coding RNA molecules, microRNA (miRNAs or miRs), able to regulate gene expression at the translation level (Huang et al., 2008, Shrivastava & Shrivastava, 2008, Sahu et al. 2007, Orlacchio et al., 2007, Williams et al., 2008, Papagiannakopoulos & Kosik, 2008). Accordingly, an increasing number of reports associate the changed expression with specific phenotypes and even with pathological conditions (Garzon & Croce, 2008, Mascellani et al., 2008, Sontheimer & Carthew, 2005, Filipowicz et al., 2005, Alvarez-Garcia & Miska, 2005). Interestingly, microRNAs play a double role in cancer, behaving both as oncogenes or tumor suppressor genes. In general, miRs promoting cancer targets mRNA coding for tumor-suppression proteins, while microRNAs exhibiting tumor-suppression properties usually target mRNAs coding oncoproteins. MicroRNAs which have been demonstrated to play a crucial role in the initiation and progression of human cancer are defined as oncogenic miRNAs (oncomiRs) (Cho, 2007). The oncomiR expression profiling of human malignancies has also identified a number of diagnostic and prognostic cancer signals (Cho, 2007, Lowery et al., 2008). Moreover, microRNAs have been firmly demonstrated to be involved in cancer metastasis (metastamiRs). Examples of metastasis-promoting microRNAs are, miR-10b (Calin et al., 2006), miR-373 and - 520c (Woods et al., 2007), miR-21, -143 and -182 (Hayashita et al., 2005; Si et al., 2007; Zhu et al.,2007). Reviews on metastamiR has been recently published Hurst et al. (Hurst et al. 2009, Edmonds et al. 2009). Reviews on metastamiRs has been recently published by Hurst et al

Multiplex Matrix Metalloproteinases Analysis in the Cerebrospinal Fluid Reveals Potential Specific Patterns in Multiple Sclerosis Patients.

Background: Matrix metalloproteinases (MMPs) are pleiotropic enzymes involved in extracellular protein degradation and turnover. MMPs are implicated in the pathogenesis of many neurological diseases, including multiple sclerosis (MS). Objective: To search the level of MMPs in the cerebrospinal fluid (CSF) of MS patients and detect possible disease-specific patterns. Methods: CSF samples from 32 MS patients and, from 15 control subjects with other inflammatory neurological diseases (OIND) were analyzed. The Bio-Plex Pro Human MMP 9-Plex Panel (Bio-Rad) was used for the quantification of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, and MMP-13. Results: CSF MMP-1 and MMP-12 levels were significantly reduced in MS as compared with OIND. In MS patients' CSF: (i) MMP-1 levels were significantly higher in women vs. men; (ii) MMP-10 concentrations were higher in patients with CSF-restricted IgG oligoclonal bands, and (iii) MMP-7 levels were increased in patients with longer disease duration. In the OIND group MMP-7 and MMP-12 levels significantly and directly correlated with age. Conclusions: Our study contributes to investigating the role of MMPs in MS, with regard to CSF immunological features and disease duration. Sex-specific differences were also detected in MMPs CSF levels

Functional analysis of novel KCNQ2 and KCNQ3 gene variants found in a large pedigree with benign familial neonatal convulsions (BFNC)

Benign familial neonatal convulsion (BFNC) is a rare autosomal dominant disorder caused by mutations in KCNQ2 and KCNQ3, two genes encoding for potassium channel subunits. A large family with nine members affected by BFNC is described in the present study. All affected members of this family carry a novel deletion/insertion mutation in the KCNQ2 gene (c.761_770del10insA), which determines a premature truncation of the protein. In addition, in the family of the proposita's father, a novel sequence variant (c.2687A>G) in KCNQ3 leading to the p.N821S amino acid change was detected. When heterologously expressed in Chinese hamster ovary cells, KCNQ2 subunits carrying the mutation failed to form functional potassium channels in homomeric configuration and did not affect channels formed by KCNQ2 and/or KCNQ3 subunits. On the other hand, homomeric and heteromeric potassium channels formed by KCNQ3 subunits carrying the p.N821S variant were indistinguishable from those formed by wild-type KCNQ3 subunits. Finally, the current density of the cells mimicking the double heterozygotic condition for both KCNQ2 and KCNQ3 alleles of the proband was decreased by approximately 25% when compared to cells expressing only wild-type alleles. Collectively, these results suggest that, in the family investigated, the KCNQ2 mutation is responsible for the BFNC phenotype, possibly because of haplo-insufficiency, whereas the KCNQ3 variant is functionally silent, a result compatible with its lack of segregation with the BFNC phenotyp

Omnivorousness in sport: The importance of social capital and networks

There has been for some time a significant and growing body of research around the relationship between sport and social capital. Similarly, within sociology there has been a corpus of work that has acknowledged the emergence of the omnivore–univore relationship. Surprisingly, relatively few studies examining sport and social capital have taken the omnivore–univore framework as a basis for understanding the relationship between sport and social capital. This gap in the sociology of sport literature and knowledge is rectified by this study that takes not Putnam, Coleman or Bourdieu, but Lin’s social network approach to social capital. The implications of this article are that researchers investigating sport and social capital need to understand more about how social networks and places for sport work to create social capital and, in particular, influence participating in sporting activities. The results indicate that social networks both facilitate and constrain sports participation; whilst family and friendship networks are central in active lifestyles, those who are less active have limited networks

Analysing the correlation between social network analysis measures and performance of students in social network-based engineering education

Social network-based engineering education (SNEE) is designed and implemented as a model of Education 3.0 paradigm. SNEE represents a new learning methodology, which is based on the concept of social networks and represents an extended model of project-led education. The concept of social networks was applied in the real-life experiment, considering two different dimensions: (1) to organize the education process as a social network-based process; and (2) to analyze the students' interactions in the context of evaluation of the students learning performance. The objective of this paper is to present a new model for students evaluation based on their behavior during the course and its validation in comparison with the traditional model of students' evaluation. The validation of the new evaluation model is made through an analysis of the correlation between social network analysis measures (degree centrality, closeness centrality, betweenness centrality, eigenvector centrality, and average tie strength) and the grades obtained by students (grades for quality of work, grades for volume of work, grades for diversity of work, and final grades) in a social network-based engineering education. The main finding is that the obtained correlation results can be used to make the process of the students' performance evaluation based on students interactions (behavior) analysis, to make the evaluation partially automatic, increasing the objectivity and productivity of teachers and allowing a more scalable process of evaluation. The results also contribute to the behavioural theory of learning performance evaluation. More specific findings related to the correlation analysis are: (1) the more different interactions a student had (degree centrality) and the more frequently the student was between the interaction paths of other students (betweenness centrality), the better was the quality of the work; (2) all five social network measures had a positive and strong correlation with the grade for volume of work and with the final graThe authors wish to acknowledge the support of the Fundacao para a Ciencia e Tecnologia (FCT), Portugal, through the Grants "Projeto Estrategico-UI 252-2011-2012'' reference PEst-OE/EME/UI0252/2011, "Ph.D. Scholarship Grant'' reference SFRH/BD/85672/2012, and the support of Parallel Planes Lda.info:eu-repo/semantics/publishedVersio

A peptide-nucleic acid targeting miR-335-5p enhances expression of cystic fibrosis transmembrane conductance regulator (CFTR) gene with the possible involvement of the CFTR scaffolding protein NHERF1

(1) Background: Up-regulation of the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) might be of great relevance for the development of therapeutic protocols for cystic fibrosis (CF). MicroRNAs are deeply involved in the regulation of CFTR and scaffolding proteins (such as NHERF1, NHERF2 and Ezrin). (2) Methods: Content of miRNAs and mRNAs was analyzed by RT-qPCR, while the CFTR and NHERF1 production was analyzed by Western blotting. (3) Results: The results here described show that the CFTR scaffolding protein NHERF1 can be upregulated in bronchial epithelial Calu-3 cells by a peptide-nucleic acid (PNA) targeting miR-335-5p, predicted to bind to the 3′-UTR sequence of the NHERF1 mRNA. Treatment of Calu-3 cells with this PNA (R8-PNA-a335) causes also up-regulation of CFTR. (4) Conclusions: We propose miR-335-5p targeting as a strategy to increase CFTR. While the efficiency of PNA-based targeting of miR-3355p should be verified as a therapeutic strategy in CF caused by stop-codon mutation of the CFTR gene, this approach might give appreciable results in CF cells carrying other mutations impairing the processing or stability of CFTR protein, supporting its application in personalized therapy for precision medicine

Role and optimization of the active oxide layer in TiO₂-based RRAM

TiO2 is commonly used as the active switching layer in resistive random access memory. The electrical characteristics of these devices are directly related to the fundamental conditions inside the TiO2 layer and at the interfaces between it and the surrounding electrodes. However, it is complex to disentangle the effects of film “bulk” properties and interface phenomena. The present work uses hard X-ray photoemission spectroscopy (HAXPES) at different excitation energies to distinguish between these regimes. Changes are found to affect the entire thin film, but the most dramatic effects are confined to an interface. These changes are connected to oxygen ions moving and redistributing within the film. Based on the HAXPES results, post-deposition annealing of the TiO2 thin film was investigated as an optimisation pathway in order to reach an ideal compromise between device resistivity and lifetime. The structural and chemical changes upon annealing are investigated using X-ray absorption spectroscopy and are further supported by a range of bulk and surface sensitive characterisation methods. In summary, it is shown that the management of oxygen content and interface quality is intrinsically important to device behavior and that careful annealing procedures are a powerful device optimisation technique

Facial emotion recognition in Williams syndrome and Down syndrome: A matching and developmental study

In this study both the matching and developmental trajectories approaches were used to clarify questions that remain open in the literature on facial emotion recognition in Williams syndrome (WS) and Down syndrome (DS). The matching approach showed that individuals with WS or DS exhibit neither proficiency for the expression of happiness nor specific impairments for negative emotions. Instead, they present the same pattern of emotion recognition as typically developing (TD) individuals. Thus, the better performance on the recognition of positive compared to negative emotions usually reported in WS and DS is not specific of these populations but seems to represent a typical pattern. Prior studies based on the matching approach suggested that the development of facial emotion recognition is delayed in WS and atypical in DS. Nevertheless, and even though performance levels were lower in DS than in WS, the developmental trajectories approach used in this study evidenced that not only individuals with DS but also those with WS present atypical development in facial emotion recognition. Unlike in the TD participants, where developmental changes were observed along with age, in the WS and DS groups, the development of facial emotion recognition was static. Both individuals with WS and those with DS reached an early maximum developmental level due to cognitive constraints

Emergence of scale-free leadership structure in social recommender systems

The study of the organization of social networks is important for understanding of opinion formation, rumor spreading, and the emergence of trends and fashion. This paper reports empirical analysis of networks extracted from four leading sites with social functionality (Delicious, Flickr, Twitter and YouTube) and shows that they all display a scale-free leadership structure. To reproduce this feature, we propose an adaptive network model driven by social recommending. Artificial agent-based simulations of this model highlight a "good get richer" mechanism where users with broad interests and good judgments are likely to become popular leaders for the others. Simulations also indicate that the studied social recommendation mechanism can gradually improve the user experience by adapting to tastes of its users. Finally we outline implications for real online resource-sharing systems